Amino acid alkylations

The advantage of trimethylsilyl (TMS) derivatives lies in the simplicity of the derivatization procedure, which is carried out by the addition of N,0-bis(trimethylsilyl)trifluoroacetamide (BSTFA) in acetonitrile and heating for approximately 2 h at 150 °C under anhydrous conditions in a sealed tube. However, there may be problems owing to the formation of multiple derivatives of each amino acid. Another technique involves the formation of n-butyl esters of the amino acids and their subsequent trimethylsilylation by a similar procedure. The n-butyl esters are formed by heating the amino acids for 15 min in n-butanol and HC1 and these are then converted to the A-TMS-n-butyl ester derivatives. A-acyl amino acid alkyl esters are commonly used. Acetylation of the butyl, methyl or propyl esters of amino acids,... 

Although the racemization of the a-carbon can now be considered a potential problem, the synthesis of 32-peptides has been achieved in the same way as seen for 33-peptides. As the 32-amino acids cannot be prepared from the analogous a-amino acids, Seebach and co-workers 5,7 opted to use Evans oxazolidinone chemistry to produce enantiomerically pure 32-amino acids. Alkylation of 3-acyloxazolidin-2-ones 17 with A-(chloromethyl)benzamide yielded the products 18 with diastereomeric ratios between 93 7 and 99 1 (Scheme 8). Removal of the chiral auxiliary (Li0H/H202) and debenzoylation (refluxing acid) was followed by ion-exchange chromatography to yield the free 32-amino acids 20 which were converted by standard means into Boc 21 or benzyl ester 22 derivatives for peptide synthesis. 

Figure 22-6. The hydrogen bond association of the L-diamide phase in its antiparaUel P-sheet conformation with (A) N-TFA-L-a-amino acid alkyl ester and (B) A-TFA-d-a-amino acid alkyl ester. (Reprinted from reference 35, with permission.)...

Amino Acids. Pseudoephedrine has been used as a chiral auxiliary for the preparation of both a-substituted and a,p-disubstituted p-amino acids. Alkylation of p-alanine was shown to furnish an efficient, inexpensive, and enantioselective route to a-alkyl p-amino acids (eq 23). ... 

This review articie provides an introduction to foided and extended conformationai motifs of synthetic peptidomimetics as tempiates for chemicai bioiogy appiications. Severai variants of these 3-dimensionai structures have been assessed, which comprise versatiie scaffoids for presentation of side-chain and main-chain peptide groups for moiecuiar recognition. Specificaiiy, reievant parameters and stereochemicai consequences are discussed for heiices of peptidomimetics based on 1) a-amino acids alkylated (e.g., methylated or ethylated) at the C"-atom 2) a,P-didehydroamino acids, in particular a,P-didehydrophenylalanine, with a carbon-carbon double bond between the a- and fS-positions 3)... 

The preferred eluents for anions are dilute carbonate-bicarbonate mixture, sodium hydroxide and, for common alkali metals and simple amines, dilute mineral acids (HCl, HNO3, BaCb, AgN03, amino acids, alkyl and aryl sulfonic acids). The most common... 

R R, R = amino-acid alkyl residues R R = H, Me, or an amino-acid... 

Solvent-free mechanochemical procedure for the synthesis of di- and tripeptides starting from Boc-protected a-amino acid Af-carboxyanhydrides (Boc-AA-NCA), a-amino acid alkyl ester hydrochlorides (HCI H-AA-OR) and NaHCOs was developed by Lamaty et al. (Scheme 3.24) [20]. Here, urethane-protected a-amino acid... 

Optimal reaction conditions were used for ball milling of stoichiometric amounts of variety of Boc-protected a-amino acid A-carboxyanhydrides (Boc-AA-NCA) 92 or Boc-protected a-amino acid A-hydroxysuccinimide esters (Boc-AA-OSu) 95 with a-amino acid alkyl ester salts (Schemes 3.26 and 3.27, Tables 3.9 and 3.10). In this way, di- to pentapeptides 97 and 100 were produced in high yield and environmentally benign manner. For some of the reactions, iBuOAc was used as a grinding auxiliary. Furthermore, it was established that no racemization could be observed as the diastereomeric excess of some products was checked and was found to be superior to 98%. After completion of Boc-AA-OSu reactions, mixture was milled for 5 min at 30 Hz with aqneous NaOH solution, diluted with EtOAc, and washed with sodium carbonate and dilnted acid. Pentapeptide Boc-Tyr(Bn)-Gly-Gly-Phe-Leu-OBn product obtained mechanochemically was successfully converted to Leu-enkephaUn by classical methods. 

H.R. Allcock, et ak. Synthesis of poly[(amino acid alkyl ester)phos-phazenes]. Macromolecules 10 (4) (1977) 824-830. 

A -dimethylaminomethylene derivatives of amino acids alkyl esters (Fig. 

Figure 15 Covalent incorporation of amino acid esters into proteins by a transpeptidation reaction catalyzed by proteases. The reaction is based on the stereospecific nucleophilic attack of the —NHj group of L-amino acid alkyl ester on the carboamide bond of the polypeptide activated by the enzyme.

Very few examples of enantioselective, calixarene-based receptors for cations have been reported so far. All of them target the ammonium head groups of chiral amines or of amino acid alkyl esters (Figure 25). 

Figure 2.6 Generic structures for amino-acid-ester-based poly(organo)phosphazenes a) amine acid ester, b) dipeptide and c) depsipeptide. and R2 = amino acid alkyl moiety, e.g., H, CH3, CH(CH3)2 and so on and R3 = either the same amino acid, another amino acid ester or indeed any other organic substituent...

Boc-protected a-amino acid AT-carboxyanhydrides or Boc-protected a-amino acid iV-hydroxysuccinimide esters with a-amino acid alkyl ester salts in the presence of NaHCOs and a minimal quantity of EtOAc led to the production of di- to pentapeptides in an efficient and environmentally benign manner. This approach was successfully applied to the synthesis of Leu-enkephalin (13GC1116). 

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